Department of Environmental Medicine, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300070, China.
School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300050, China.
Oncol Res. 2023 Jun 27;31(4):481-493. doi: 10.32604/or.2023.029064. eCollection 2023.
Oral squamous cell carcinoma (OSCC) is a common malignant tumor. Recently, Laminin Gamma 2 (LAMC2) has been shown to be abnormally expressed in OSCC; however, how LAMC2 signaling contributes to the occurrence and development of OSCC and the role of autophagy in OSCC has not been fully explored. This study aimed to analyze the role and mechanism of LAMC2 signaling in OSCC and the involvement of autophagy in OSCC.
To explore the mechanism by which LAMC2 is highly expressed in OSCC, we used small interfering RNA (siRNA) to knock down LAMC2 to further observe the changes in the signaling pathway. Furthermore, we used cell proliferation assays, Transwell invasion assays, and wound-healing assays to observe the changes in OSCC proliferation, invasion, and metastasis. RFP-LC3 was used to detect the level of autophagy intensity. A cell line-derived xenograft (CDX) model was used to detect the effect of LAMC2 on tumor growth .
This study found that the level of autophagy was correlated with the biological behavior of OSCC. The downregulation of LAMC2 activated autophagy and inhibited OSCC proliferation, invasion, and metastasis via inhibiting the PI3K/AKT/mTOR pathway. Moreover, autophagy has a dual effect on OSCC, and the synergistic downregulation of LAMC2 and autophagy can inhibit OSCC metastasis, invasion, and proliferation via the PI3K/AKT/mTOR pathway.
LAMC2 interacts with autophagy to regulate OSCC metastasis, invasion, and proliferation via the PI3K/AKT/mTOR pathway. LAMC2 down-regulation can synergistically modulate autophagy to inhibit OSCC migration, invasion, and proliferation.
口腔鳞状细胞癌（OSCC）是一种常见的恶性肿瘤。最近，层粘连蛋白γ 2（LAMC2）在 OSCC 中表现出异常表达；然而，LAMC2 信号如何促进 OSCC 的发生和发展，以及自噬在 OSCC 中的作用尚未得到充分探索。本研究旨在分析 LAMC2 信号在 OSCC 中的作用和机制以及自噬在 OSCC 中的参与。
为了探讨 LAMC2 在 OSCC 中高表达的机制，我们使用小干扰 RNA（siRNA）敲低 LAMC2 进一步观察信号通路的变化。此外，我们使用细胞增殖测定、Transwell 侵袭测定和划痕愈合测定观察 OSCC 增殖、侵袭和转移的变化。使用 RFP-LC3 检测自噬强度水平。使用细胞系衍生的异种移植（CDX）模型检测 LAMC2 对肿瘤生长的影响。
本研究发现自噬水平与 OSCC 的生物学行为相关。LAMC2 的下调通过抑制 PI3K/AKT/mTOR 通路激活自噬并抑制 OSCC 的增殖、侵袭和转移。此外，自噬对 OSCC 具有双重作用，LAMC2 和自噬的协同下调通过 PI3K/AKT/mTOR 通路抑制 OSCC 转移、侵袭和增殖。
LAMC2 通过 PI3K/AKT/mTOR 通路与自噬相互作用调节 OSCC 的转移、侵袭和增殖。LAMC2 的下调可以协同调节自噬抑制 OSCC 的迁移、侵袭和增殖。
